Abstract 4788
Background
Tumor mutational burden (TMB) is associated with genome instability and immunogenicity, which has been reported to play an important role in predicting the efficacy of immune checkpoint inhibitors. However, the relationship of TMB and prognosis in solid tumors is not yet fully understood. In this study, we aimed to explore the association between TMB and prognosis across pan-cancers.
Methods
Whole-exome sequencing from 7882 solid tumors, spanning 22 cancer types from The Cancer Genome Atlas were analyzed. TMB was defined by total non-silent somatic mutation counts in coding region. Patients were classified into four groups based on the quartiles of TMB in each tumor. All Hazard ratios (HR) were reported as the risk ratio of the top 25% to the bottom 25% group.Table: 57PD
The associations of TMB and OS across pan-cancers
| tumor | full names | TMB-median (interquartile) | ALL | Stage I-II | Stage III-IV | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| N | HR(95% CI) | P | N | HR(95% CI) | P | N | HR(95% CI) | P | |||
| BLCA | Bladder Urothelial Carcinoma | 151(85-269) | 408 | 0.51(0.33-0.78) | <0.001 | 131 | 1.07(0.45-2.55) | 0.89 | 275 | 0.41(0.24-0.68) | <0.001 |
| BRCA | Breast invasive carcinoma | 39(26-69) | 970 | 1.48(0.87-2.54) | 0.15 | 720 | 0.98(0.49-1.94) | 0.95 | 229 | 4.46(1.57-12.69) | <0.001 |
| CHOL | Cholangiocarcinoma | 32(26-44) | 41 | 1.37(0.35-5.32) | 0.65 | 28 | 2.33(0.44-12.49) | 0.32 | (-) | (-) | (-) |
| COAD | Colon adenocarcinoma | 111(82-167) | 378 | 1.43(0.79-2.58) | 0.24 | 202 | 3.24(0.93-11.37) | 0.07 | 165 | 1.57(0.7-3.5) | 0.27 |
| ESCA | Esophageal carcinoma | 100(77-144) | 183 | 1.84(0.98-3.48) | 0.06 | 97 | 3.01(1.18-7.68) | 0.02 | 63 | 1.07(0.36-3.14) | 0.90 |
| GBM | Glioblastoma multiforme | 47(37-64) | 385 | 1.01(0.73-1.42) | 0.93 | (-) | (-) | (-) | (-) | (-) | (-) |
| HNSC | Head and Neck squamous cell carcinoma | 92(60-140) | 506 | 1.65(1.11-2.45) | 0.01 | 96 | 3.94(1.34-11.59) | 0.01 | 341 | 1.11(0.69-1.78) | 0.66 |
| KIRC | Kidney renal clear cell carcinoma | 48(35-63) | 333 | 3.72(1.79-7.75) | <0.001 | 222 | 8.23(1.9-35.6) | <0.001 | 109 | 1.82(0.75-4.38) | 0.18 |
| KIRP | Kidney renal papillary cell carcinoma | 54(35-73) | 277 | 0.39(0.13-1.15) | 0.09 | 187 | 1.17(0.19-7.04) | 0.86 | 63 | (-) | (-) |
| LGG | Brain Lower Grade Glioma | 25(18-34) | 501 | 5.03(2.87-8.8) | <0.001 | (-) | (-) | (-) | (-) | (-) | (-) |
| LIHC | Liver hepatocellular carcinoma | 77(55-107) | 357 | 1.5(0.88-2.53) | 0.13 | 250 | 1.87(0.87-3.98) | 0.11 | 86 | 1.36(0.61-3.05) | 0.45 |
| LUAD | Lung adenocarcinoma | 171(74-338) | 501 | 0.83(0.54-1.28) | 0.39 | 390 | 0.89(0.52-1.52) | 0.67 | 104 | 0.69(0.33-1.46) | 0.33 |
| LUSC | Lung squamous cell carcinoma | 205(148-297) | 483 | 0.75(0.52-1.09) | 0.13 | 390 | 0.7(0.46-1.06) | 0.09 | 89 | 0.92(0.38-2.21) | 0.84 |
| OV | Ovarian serous cystadenocarcinoma | 79(53-130) | 429 | 0.73(0.52-1.03) | 0.08 | (-) | (-) | (-) | (-) | (-) | (-) |
| PAAD | Pancreatic adenocarcinoma | 35(25-46) | 173 | 1.62(0.88-3.02) | 0.12 | (-) | (-) | (-) | (-) | (-) | (-) |
| READ | Rectum adenocarcinoma | 95(74-127) | 127 | 0.68(0.21-2.27) | 0.53 | 61 | 1.22(0.11-13.47) | 0.87 | 58 | 0.6(0.1-3.72) | 0.59 |
| SARC | Sarcoma | 40(27-54) | 235 | 1.25(0.63-2.49) | 0.52 | (-) | (-) | (-) | (-) | (-) | (-) |
| SKCM | Skin Cutaneous Melanoma | 226(62-415) | 103 | 0.45(0.15-1.3) | 0.14 | 67 | 0.14(0.01-1.32) | 0.09 | 31 | 1.51(0.36-6.32) | 0.58 |
| STAD | Stomach adenocarcinoma | 106(66-216) | 409 | 0.52(0.34-0.8) | <0.001 | 178 | 0.45(0.2-0.98) | 0.05 | 214 | 0.53(0.31-0.92) | 0.02 |
| THCA | Thyroid carcinoma | 9(6-13) | 488 | 6.92(0.85-56.28) | 0.07 | 325 | (-) | (-) | 161 | 1.34(0.16-11.19) | 0.79 |
| UCEC | Uterine Corpus Endometrial Carcinoma | 89(47-562) | 527 | 0.27(0.13-0.57) | <0.001 | (-) | (-) | (-) | (-) | (-) | (-) |
| UVM | Uveal Melanoma | 12(9-15) | 68 | 2.5(0.45-13.88) | 0.29 | 37 | (-) | (-) | 30 | 2.4(0.19-30.98) | 0.50 |
Results
Among 22 tumors, the level of TMB of top five tumors (median, interquartile, sample size) were: SKCM (226, 62-415, 103), LUSC (205, 148-297, 483), LUAD (171, 74-338, 501), BLCA (151, 85-269, 408), COAD (111, 82-167, 378). In all patient analyses of each tumor, higher TMB was associated with longer overall survival (OS) in BLCA, STAD and UCEC, and was associated with shorter OS in HNSC, KIRC and LGG. In stage I-II of each tumor, higher TMB was significantly associated with prolonged OS in STAD, but with shorter OS in ESCA, HNSC and KIRC. In stage III-IV of each tumor, higher TMB was significantly associated with prolonged OS in BLCA and STAD, but with shorter OS in BRCA. In 5 tumors (including BLCA, HNSC, KIRC, LUSC and THCA), patients with higher pathological stage had significantly higher TMB (P < 0.05). However, only in COAD and READ, patients with higher stage had significantly lower TMB (P < 0.05).
Conclusions
Higher TMB played different roles in various tumors, which may be attribute to different driver mutations or other factors. Further analyses of underlying mechanism were underway to confirm and explore the potential prognosis prediction of TMB across pan-cancers.
Clinical trial identification
Legal entity responsible for the study
Feng Qiu.
Funding
Has not received any funding.
Editorial Acknowledgement
Disclosure
All authors have declared no conflicts of interest.